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As a toxic heavy metal, lead (Pb) is well known for impairment of renal function due to oxidative injuries. In contrast, the antioxidant activity of silibinin has been approved. Given the role of silibinin antioxidant activity, the present study investigated the effectiveness of silibinin-loaded nanostructured lipid carriers (Sili-NLCs) against Pb-induced acute nephrotoxicity in rats. The emulsification-solvent evaporation method was applied to prepare Sili-NLCs. Sixty male Wistar rats were divided into ten separate groups. Pb (20 mg/kg/day, i.p.) was applied to induce nephrotoxicity and in the treatment groups animals received the same concentration of silibinin and Sili-NLCs (25, 50, and 100 mg/kg/day, p.o.) for five days. After sacrificing rats, kidney tissue samples were collected to assess the oxidative stress parameters, including lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity. Also, histopathological examination using Hematoxylin-Eosin (H&E) was studied. Not only did Pb injection significantly increase the renal levels of LPO and NO, but also decreased the levels of antioxidant enzyme activity. On the other hand, Sili-NLCs were more effective than silibinin in decreasing renal oxidative damage by increasing the antioxidant defense system. Moreover, the histopathological examination correlated well with biochemical findings. Our data suggested that Sili-NLCs are potentially superior to pure silibinin for attenuating Pb-induced acute nephrotoxicity., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests. Ethical approval Animal experiment working methods were approved based on animal care and use methods by the Ethics Committee of HUMS under the code of IR.UMSHA.REC.1399.648., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective . The purpose of this study is to develop, optimize, and evaluate the in vivo effectiveness of orally administered silibinin-loaded nanostructured lipid carriers (SB-NLCs) in amyloid β-induced Alzheimer's disease in Wistar rats. Methods . The emulsification-solvent evaporation method was used for preparing the NLCs, using stearic acid, triacetin, and Cremophor® RH40. The statistical optimization of SB-NLCs was done using the Box-Behnken design (BBD). Then, the following parameters were evaluated: zeta potential, average size, in vitro drug release, and drug entrapment efficiency. Physicochemical properties of the optimized SB-NLCs were determined by FTIR, DSC, and P-XRD. The behavioral (OFT, NOR, MWM), histological (H&E, Congo Red), and biochemical (TAC, MDA, GSH) tests were conducted on 48 male Wistar rats. Results . The findings showed that the mean particle size, zeta potential and entrapment efficiency of optimized SB-NLCs were 194.71 ± 14.06 nm, -12.46 ± 0.25 mV, and 72.13% ± 1.41, respectively. XRD and DSC studies confirmed a reduction in the crystallinity of SB which occurred due to its embedment in the nanostructured lipid. The FTIR results indicated the lack of existence of any chemical interaction between the carrier components and the drug. Drug release in the external environment was slow and steady. Drug-containing nanoparticles showed good stability during three months of storage at 4 °C. The behavioral test of OFT showed no significant change between groups. The group treated with SB-NLCs showed a markedly higher discrimination rate compared to the Aβ group ( p < 0.001). The time of the SB-NLC treated group in the target area was considerably more than the time of the SB and Aβ groups, respectively ( p < 0.01, p < 0.001), in the MWM test. Histological and biochemical analysis revealed better results in the SB-NLC group as against the SB group. Conclusion . SB-NLCs can be considered as a promising formulation for the proper treatment of Alzheimer's disease in the oral drug delivery system.

Aim: To investigate comparative in vitro and in vivo performance of lipid vesicular and particulate systems in escalating oral bioavailability for superior hepatoprotection., Materials and Methods: Systems were fabricated using easy to scale up process and novel excipients to deliver Silibinin. In vitro characterization followed by pharmacokinetic and pharmacodynamic evaluation in rats was conducted to establish a correlation., Results: Nanoformulations resulted in 20 fold increase in solubilisation and significant increase in permeation. 2.5 fold increase in bioavailability was evident in vivo. Vesicles demonstrated greatest hepatoprotective potential in efficacy study., Conclusion: The findings establish a link between in vitro and in vivo performance to rank order lipid nanoartchitects. Concurrently, a significant potential in therapeutic intervention of hepatotoxicity is envisaged as elucidated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Silybin (Sb) is the major flavolignan of the extract of Silybum marianum. It is used for the treatment of various acute and chronic liver toxicities, inflammation, fibrosis and oxidative stress. Many studies indicate that Sb is also active against different carcinomas and it has been very recently proposed to be beneficial in type 2 diabetes patients. However, Sb is a low water soluble and low permeable compound., Objective: In this study, Solid Lipid Nanoparticles (SLNs) were proposed to enhance the solubility and the intestinal absorption of Sb., Methods: SLNs were made of stearic acid and Brij 78 and subsequently coated with chitosan. Formulations were physically and chemically characterized. Stability studies were also assessed. Sb in vitro release was evaluated in different pH media. In vitro permeability test with artificial membranes and Caco-2 cells were performed. Cellular uptake and mucoadhesion studies were conducted., Results: Both nanoparticles were found to be stable. In vitro release indicated that SLNs may prevent burst release and gastric degradation of Sb. Higher extent of Sb permeation was observed for both nanoparticles in PAMPA and Caco-2 cell monolayer models. The results of the cellular uptake study suggested the involvement of active endocytic processes. Chitosan significantly improves mucoadhesion properties of nanoparticles., Conclusions: Together with the excellent stability, strong mucoadhesive property, and slow release, chitosan coated SLNs demonstrated promising potential to enhance absorption of hydrophobic Sb after oral administration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A selective acylation protocol using cerium chloride (CeCl₃) as catalyst was applied to functionalize silybinin ( 1 ), a natural antioxidant flavonolignan from milk thistle fruit, in order to increase its solubility in lipophilic media while retaining its strong antioxidant activity. The selective esterification of 1 at the position 3-OH with a palmitate acyl chain leading to the formation of the 3- O -palmitoyl-silybin ( 2 ) was confirmed by both mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses. The antioxidant activity of 1 was at least retained and even increased with the CUPRAC assay designed to estimate the antioxidant activity of both hydrophilic and lipophilic compounds. Finally, the 3- O -palmitoylation of 1 , resulting in the formation of 2 , also increased its anti-lipoperoxidant activity (i.e., inhibition of conjugated diene production) in two different lipophilic media (bulk oil and o / w emulsion) subjected to accelerated storage test.